Evolving Real-World Effectiveness of Monoclonal Antibodies for Treatment of COVID-19 : A Cohort Study.

BACKGROUND

Treatment guidelines and U.S. Food and Drug Administration emergency use authorizations (EUAs) of monoclonal antibodies (mAbs) for treatment of high-risk outpatients with mild to moderate COVID-19 changed frequently as different SARS-CoV-2 variants emerged.

OBJECTIVE

To evaluate whether early outpatient treatment with mAbs, overall and by mAb product, presumed SARS-CoV-2 variant, and immunocompromised status, is associated with reduced risk for hospitalization or death at 28 days.

DESIGN

Hypothetical pragmatic randomized trial from observational data comparing mAb-treated patients with a propensity score-matched, nontreated control group.

SETTING

Large U.S. health care system.

PARTICIPANTS

High-risk outpatients eligible for mAb treatment under any EUA with a positive SARS-CoV-2 test result from 8 December 2020 to 31 August 2022.

INTERVENTION

Single-dose intravenous mAb treatment with bamlanivimab, bamlanivimab-etesevimab, sotrovimab, bebtelovimab, or intravenous or subcutaneous casirivimab-imdevimab administered within 2 days of a positive SARS-CoV-2 test result.

MEASUREMENTS

The primary outcome was hospitalization or death at 28 days among treated patients versus a nontreated control group (no treatment or treatment ≥3 days after SARS-CoV-2 test date).

RESULTS

The risk for hospitalization or death at 28 days was 4.6% in 2571 treated patients and 7.6% in 5135 nontreated control patients (risk ratio [RR], 0.61 [95% CI, 0.50 to 0.74]). In sensitivity analyses, the corresponding RRs for 1- and 3-day treatment grace periods were 0.59 and 0.49, respectively. In subgroup analyses, those receiving mAbs when the Alpha and Delta variants were presumed to be predominant had estimated RRs of 0.55 and 0.53, respectively, compared with 0.71 for the Omicron variant period. Relative risk estimates for individual mAb products all suggested lower risk for hospitalization or death. Among immunocompromised patients, the RR was 0.45 (CI, 0.28 to 0.71).

LIMITATIONS

Observational study design, SARS-CoV-2 variant presumed by date rather than genotyping, no data on symptom severity, and partial data on vaccination status.

CONCLUSION

Early mAb treatment among outpatients with COVID-19 is associated with lower risk for hospitalization or death for various mAb products and SARS-CoV-2 variants.

PRIMARY FUNDING SOURCE

None.